Mesoporous silica (Si-MP) is a porous structure that allows the encapsulation of substrates in the pores, and its surface can be chemically modified. These properties were applied to use Si-MP as a versatile hybrid material for catalysis, drug delivery, and imaging. Furthermore, chemical modification of Si-MP enables the design of signal-responsive matrices for the controlled release of substrates from the pores of the matrices.
Different stimuli such as pH [2-5] photonic signals [6, 7], redox-reagents [8-10] or enzymes [11-14] were implemented to trigger the opening of the pores, leading to the controlled release of encapsulated substrates. Accordingly, the pores of the Si-MP were capped with gate units that lock the substrate in the pores, and allow the stimuli-responsive unlocking of the gates and the release of the substrates. For example, the photonic dethreading of semi-rotaxane pore-capping nanostructures were implemented to open the pores and release the stored substrate[15, 16].
The information encoded in the base sequences of nucleic acids provides a rich arena of opportunities to develop the area of DNA nanotechnology. Sequence-guided and pH-stimulated assembly of single-stranded DNA into i-motif structures or the cooperative binding of DNA duplexes by metal ions, e.g., by T-Hg2+-T bridges were implemented to develop different DNA machines [17-19] and to develop logic gates [20, 21] and finite state logic machines [22]. Similarly, sequence-specific nucleic acid strands reveal specific binding properties toward low-molecular-weight or macromolecular substrates (aptamers) [23-25] or exhibit catalytic properties (DNAzymes) [26-29]. Aptamers have been implemented to develop DNA machines [30, 31] or to assemble programmed nanostructures, [32-34] and catalytic nucleic acids were used to develop logic gates, and logic gate cascades [35-37].
The conjugation of nucleic acids to mesoporous SiO2 enabled the implementation of the signal-triggered functions of the DNA to “lock” and “unlock” the pores of the SiO2. For example, the pores were loaded with a dye-substrate and “locked” by i-motif, C-quadruplex, capping units, and subsequently “unlocked” by separation of the bulky i-motif structure, to random single strand, at neutral pH values, thus allowing the release of the substrates [38]. In a related system the change of the pH and the opening of the pores was stimulated by a photochemical process.[39] Alternatively, the pores of the mesoporous SiO2 were capped with duplex DNA units and the capping strands were separated by a strand displacement process, in the presence of Hg2+ ions, to yield a T-Hg2+-T bridged duplex structure of enhanced stability. The release of the pore-entrapped substrate, enabled the fluorescence detection of Hg2+-ions [40].
It would be a major advance if one could design gated systems where the biocatalytic process is activated by a primary sensing or recognition event of an analyte or biomarker of particular interest, to ensure safe and efficient drug delivery to specific sites.